L26/P-873 From eggs to babies: outlining the competence of each single oocyte and the impact of intrinsic and extrinsic factors

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Abstract Study question Which intrinsic and extrinsic factors influenced the oocyte-to-baby rate across 11 years over an IVF clinic? Summary answer The overall oocyte-to-baby rate was 7.7%±14.2%, ranging between 13.3%±15.7% for women <35yr in absence of severe-male-factor and 0.7%±2.7% for women ≥42yr in presence of severe-male-factor. What is known already Over the past decades, major clinical and laboratory advances have reshaped the IVF journey, including personalized ovarian stimulation, blastocyst culture, vitrification, single embryo-transfer, time-lapse incubation, trophectoderm biopsy and chromosomal testing. Nevertheless, despite all these refinements, IVF success remains biologically constrained: current criteria scarcely predict and current interventions cannot modify the inherent reproductive potential of each gamete. In this context, accurately weighting the expected competence of each oocyte becomes essential for personalized patient counselling and decision-making across all IVF journey, including fertility preservation. Study design, size, duration Retrospective analysis of 5793 couples undergoing their first oocyte-retrieval with ≥1 MII-oocyte between 2010-2020 at a private clinic. All oocytes retrieved were inseminated. DuoStim were excluded. Oocyte-to-baby rate were calculated as the true number of live-births achieved among transferred embryos (true-LBs) plus the number of live-births estimated among surplus vitrified embryos (estimated-LBs) divided by all MII-oocytes retrieved from each couple. Sub-analyses were conducted per ranges of maternal age and presence/absence of severe-male-factor (SMF). Participants/materials, setting, methods All patients underwent natural-cycle or conventional-stimulation, ICSI, cleavage/blastocyst-culture in conventional/time-lapse incubators, and fresh/vitrified-warmed untested/euploid single embryo transfer. SMF was defined as oligoasthenoteratozoospermia or azoospermia. Estimated-LBs were calculated by applying the true LB-rates achieved to the number of surplus vitrified embryos as follows: 37-47% for euploid blastocysts, 3-28% and 10-32% for untested cleavage-stage embryos and blastocysts, respectively, across ranges of maternal age and year. Linear regressions outlined associations among all clinical variables and oocyte-to-baby rate. Main results and the role of chance Median maternal age was 38yr and AMH 1.6ng/ml. SMF prevalence was 19%. Overall, 37514 MII-oocytes were retrieved resulting in 2075 LBs. From 2912 surplus vitrified embryos, we estimated additional 983 LBs. The oocyte-to-baby rate was 7.7±14.2% per patient. Each additional year in maternal-age involved a 0.9%-decrease in this outcome (95%CI:-0.8% to -1%,p<0.001). Indeed, when stratified by range, a progressive decline was reported: 12.7%±15.5% in women <35yr, 10.2%±16% at 35-37yr, 8%±13.8% at 38-39yr, 4.7%±12.5% at 40–41yr, 1.9±8.6% at ≥ 42yr (p < 0.001). Notably, the limited decrease in the range 35 to 39yr has implications for fertility-preservation age thresholds. SMF involved a further 2%-decrease (95%CI:-2.9% to -1%, p < 0.001) beyond maternal age. No association with the oocyte-to-baby rate was observed for ovarian-stimulation, gonadotrophins daily dose, use of LH-activity, length of stimulation, and type of ovulation-induction. Similarly, extended culture to blastocyst, media and incubators used, freeze-all, and aneuploidy testing showed no impact. In fact, the year when each treatment was conducted across the 11 years of the study period, was associated with the oocyte-to-baby rate only from a univariate analysis (0.1%-increase per year; 95%CI:0 to + 0.2%, p = 0.043). Thus, this outcome is a very stable endpoint when safe and validated strategies, protocols and devices are implemented. Limitations, reasons for caution Retrospective study. Estimates for surplus vitrified embryos entail stage of transfer, whether embryos were euploid/untested, and year of treatment, but did not incorporate embryo quality, timing of blastulation, or patient-specific factors (e.g., BMI, endometrial characteristics). Moreover, they represent ca.30% of the LBs achieved. Wider implications of the findings Each oocyte is characterized by an inherent chance of LB, mostly modulated by maternal age and SMF. Oocyte-to-baby rate is therefore critical for decision-making in reproductive medicine, but also a meaningful key-performance-indicator. Constant performance, if not improvements, are expected, when new equipment, protocols or strategies are introduced in IVF practice. Trial registration number No

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